Microstructure, Content and in vitro Release of Brucine and Strychnine in Strychnos Nux-Vomica Powder with Different Particle Sizes

To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepared.Microstructures and particle sizes were analyzed, and high performance liquid chromatography(HPLC) was used to test the contents and in vitro release performances of brucine and strychnine in the samples. Results showed that the contents and the in vitro release rates of brucine(or strychnine) in different samples were different since there are different proportions of endosperms to epidermal cells in Strychnos nux-vomica powder with different particle sizes. Brucine and strychnine in each sample were promptly released in the first ten minutes and their cumulative release rates were higher than 70% after ten minutes. Eighty minutes later, the cumulative release rate tended to be a constant. Considering the quality uniformity and safety of Strychnos nux-vomica powder used as traditional Chinese medicine, it would be better to control the particle size of Strychnos nux-vomica powder between 100 and 140 mesh in which the maximum cumulative release rate in vitro of brucine and strychnine can be relatively low within this range.

马钱子中毒引起癫痫发作患者的远期预后

目的观察马钱子中毒所致癫痫患者的远期预后及对其生活质量的影响,探索其防治规律。方法对误服马钱子中毒引起癫痫发作的患者在总结其临床规律后进行长时间定期随访,观察患者的生存、认知、情感活动的变化和疾病治疗谱。结果 5例中有2例在随访中死亡,存活者中1例有明显的认知障碍和忧郁,1例合并有非痫性发作多次导致误诊误治,1例在癫痫得到控制后脑电图上仍有明显的痫样放电;几乎均对目前所使用的抗癫痫药物都存在不同程度的耐药。结论马钱子所致癫痫是一种耐药性癫痫,癫痫发作对患者的生活质量有明显的影响。

不同载药形式的肉桂油对马钱子总碱中马钱子碱和士的宁体外透皮吸收的影响

目的:研究不同载药形式的肉桂油对马钱子总碱中马钱子碱和士的宁体外透皮吸收的影响。方法:以大鼠离体皮肤为实验材料,采用Franz扩散池法,以高效液相色谱法(HPLC)测定马钱子总碱中马钱子碱和士的宁48 h的累积渗透量(Q_(48 h))、稳态渗透速率常数(Jss)、增渗倍数(ER)和累积透过率(T),考察不同载药形式(溶液、微乳、脂质体、传递体、醇传递体)的肉桂油对马钱子总碱中马钱子碱和士的宁体外透皮吸收的影响,并以不加肉桂油的马钱子总碱为对照进行比较。结果:肉桂油以溶液、微乳、脂质体、传递体和醇传递体不同载药形式入药后马钱子碱的Q_(48 h)分别为(334.44±7.65)、(265.33±7.54)、(249.12±6.60)、(202.24±24.55)、(274.30±17.12)μg/cm^2;Jss分别为25.07、21.62、19.73、17.31、24.86μg/(cm^2·h),ER分别为5.2、4.5、4.1、3.6、5.1,T分别为55.12%、43.73%、41.06%、33.33%、45.22%;士的宁的Q_(48 h)分别为(395.37±2.90)、(285.13±6.69)、(298.26±12.54)、(272.26±13.32)、(338.70±9.41)μg/cm2;Jss分别为32.91、23.80、26.04、22.76、29.26μg/(cm2·h),ER分别为2.0、1.5、1.6、1.4、1.8,T分别为25.54%、18.42%、19.27%、17.59%、21.88%。与不加肉桂油比较,加入肉桂油能明显增加马钱子总碱中士的宁和马钱子碱的Q_(48 h)(P<0.05)。结论:不同载药形式的肉桂油均能促进马钱子总碱中士的宁和马钱子碱的透皮吸收,其中以溶液形式最明显。

基于斑马鱼模型探讨马钱子的抗血管生成活性

目的:以斑马鱼为模型,探讨马钱子的抗血管生成活性。方法:以Tg(kdrl:mCherry)斑马鱼和野生斑马鱼为模型,在安全浓度范围内,分别采用荧光显像和体内碱性磷酸酶定量检测的方法,以PTK787为阳性对照,考察马钱子水提取物对斑马鱼血管生成的抑制作用。结果:与空白对照组比较,在一定的浓度范围内,低浓度的马钱子水提取物能抑制Tg(kdrl:mCherry)斑马鱼的节间血管生成,随着提取物浓度的增加抑制作用更加明显,抑制作用呈剂量依赖性。在碱性磷酸酶定量检测实验中,马钱子水提取物浓度为25μg·mL^(-1)时,血管生成抑制率为8.61%;浓度为100μg·mL^(-1)时,血管生成抑制率为26.16%;在一定的浓度范围内,马钱子处理组均表现出显著的抗血管生成活性(P<0.05),血管生成抑制率与马钱子水提取物浓度成线性关系。结论:马钱子水提取物可以有效的抑制斑马鱼血管生成,有明显的抗血管生成活性。

Chemical constituents from processed seeds of Strychnos nux-vomica

Fifteen compounds were isolated from the processed seeds of Strychnos nux-vomica and were identified as follows：strychnine（1）,brucine（2）,pseudostrychnine（3）,pseudobrucine（4）,secoxyloganin（5）,caffeic acid（6）,p-hydroxybenzoic acid（7）,p-hydroxyphenylacetic acid（8）,uvaol（9）,stigmasta-7,22,25-triene-3-ol（10）,lupeol（11）,11-oxo-α-amyrin palmitate（12）,catechol（13）,maltol（14）,adenosine（15）.Compounds 5-15 were isolated from genus Strychnos for the first time.

Zebrafish model for assessing induced organ toxicity by Strychnos nux-vomica

OBJECTIVE:To assess the acute organ toxicity of Strychnos nux-vomica with zebrafish model visually.METHODS:To assess acute toxicity,we initially determined the lethal concentration after Strychnos nux-vomica treatment for 24 h.Zebrafish was treated with five concentrations Strychnos nux-≦vo LC10 for 24 h,and the effects ofmica on morphology,function of heart,central nervous system,liver,kidney and organ-specific cell death were assessed.Next,we assessed the reversibility of toxic effect.RESULTS:Strychnos nux-vomica has an effect on the different organs of zebrafish,including heart,central nervous system,liver,and kidney,and cadiotoxicity induced by Strychnos nux-vomica was reversible to some extent.CONCLUSION:Zebrafish model is suitable for confirming the toxic target organs for Chinese traditional medicine.

马钱子的毒性研究进展

马钱子有较明显的药效,在临床及民间多有应用,但因马钱子治疗剂量与中毒剂量较接近,其临床应用的毒副反应报道也多,限制了马钱子的广泛使用。马钱子在治疗各种疾病中疗效肯定,是具有较大开发潜力的中药。文章回顾和分析了近年来研究有毒中药马钱子的文献,总结并归纳马钱子在化学成分、毒理学、药代动力学、减毒增效方面的研究进展,为今后深入进行中药毒性,特别是马钱子的毒性研究提供相关的依据,并针对马钱子减毒增效的机制为马钱子的临床应用提供了合理性的建议。

Effect of Baizhu(Rhizoma Atractylodis Macrocephalae)extract on intestinal absorption of brucine and strychnine in vitro and in situ

OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mechanism of these effects.METHODS:The apparent permeability value(Papp)and absorption rate constant(Ka)were chosen as indices.The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine.To confirm the results,the brucine and strychnine concentrations in hepatic portal venous blood were determined.Western blotting was used to study P-glycoprotein(P-gp)expression in the Caco-2 cell line.RESULTS:Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor,but no significant increase was noted in the presence of a tight junction regulator.The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression.CONCLUSION:The primary absorption mechanism for brucine and strychnine is passive transport,which is affected by P-gp.